Impact of Muscle Afferent Feedback During Exercise in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Impact of Somatosensory Feedback on Peripheral Muscle Fatigue and Exercise Tolerance in Patients With COPD

Recently, direct evidences point to the contributing role of peripheral muscle fatigue in exercise tolerance among patients with COPD. However, the physiological mechanisms by which peripheral muscle fatigue impairs exercise tolerance are still unknown, as factors regulating peripheral muscle fatigue in COPD may be complex. One possible link between limb muscle fatigue and exercise intolerance could be enhanced afferent signals from the active limb muscles to the central command, thereby limiting central motor output and eventually leading to exercise termination.

A direct method to investigate the regulation of peripheral muscle fatigue during exercise in patients with COPD is the blockade of peripheral neural afferents via lumbar anesthesia. Consequently, investigating the interplay between the peripheral muscular component and the central motor command during self-paced exercise could shed light on the regulation of peripheral muscle fatigue in COPD and its implication in exercise intolerance.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Fentanyl; Drug: Placebo comparator

Detailed Description

The aim of the study is to characterize the role of peripheral muscle afferents on the development of muscle fatigue, cardiorespiratory response and exercise tolerance to constant-workrate endurance cycling exercise in patients with COPD.

In a double-blind randomized design, patients with GOLD stage II-III COPD will be recruited and will complete a constant-workrate cycling test following either the injection of a placebo [NaCl, interspinous L2-L3] or an opioid [Fentanyl 25 µg, intrathecal L2-L3] inhibiting central feedback of peripheral muscles sensory afferents. Quadriceps force (TwQ) will be measured by magnetic stimulation of the femoral nerve and central chemoreceptors response will be assessed by CO2 rebreathing, both performed before and after the injection. Finally, TwQ will also be measured after the endurance cycling test to assess the magnitude of quadriceps fatigue induced by symptom-limited exercise.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Institut universitaire de cardiologie et de pneumologie de Quebec - Universite Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Smoking history > 15 pack-years
• COPD GOLD II-III (30 % predicted < FEV1 < 80 % predicted; FEV1/FVC < 0.70)

Exclusion Criteria:

• Unstable condition
• Recent exacerbation (<3 months)
• Recent cancer (<3 months)
• Myopathy, neuromuscular disease
• Unstable cardiac disease
• Hepatic, kidney, intestinal disease
• BMI > 35
• PaCO2 > 45 mmHg
• PaO2 < 60 mmHg

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo comparator; placebo [NaCl]
Experimental: Fentanyl	Drug: Fentanyl; Single-dose of intrathecal fentanyl [25ug] Duration of fentanyl : 3.5 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endurance time	Exercise tolerance is referred as the endurance time (sec) during constant-workrate cycling test at 80 % of the predetermined maximal workload in every conditions (placebo and fentanyl)	60-min post-anesthesia - From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory response	The ventilatory response (Ventilation, L/min) will be monitored continuously during the cycling test and will be compared between the two conditions (placebo vs. fentanyl)	60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)
Quadriceps muscle fatigue	The quadriceps muscle fatigue will be monitored before and after the cycling test to quantify the extent of muscle fatigue produced by the cycling test. This will be done by magnetic stimulation of the femoral nerve and maximal voluntary contraction. Also, non-invasive surface electromyography (EMG) of the quadriceps will help to better characterize muscle fatigue.	15-min after the end of constant-workload cycling test
Dynamic hyperinflation	Dynamic hyperinflation will be monitored periodically every 2-min during the cycling test by manoeuvres of inspiratory capacity and will be compared between the two conditions (placebo vs. fentanyl)	60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise
Effort perception	Leg fatigue and dyspnea perception (Borg scale scores) will be monitored periodically every 2-min during the cycling test and will be compared between the two conditions (placebo vs. fentanyl)	60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise

Collaborators and Investigators

• Sponsor: Laval University
• Investigators: Principal Investigator: François Maltais, MD, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Publications and helpful links

General Publications

• Gagnon P, Bussieres JS, Ribeiro F, Gagnon SL, Saey D, Gagne N, Provencher S, Maltais F. Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012 Oct 1;186(7):606-15. doi: 10.1164/rccm.201203-0404OC. Epub 2012 Jul 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: January 20, 2012
• First Submitted That Met QC Criteria: January 27, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): February 1, 2012
• Last Update Submitted That Met QC Criteria: January 27, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Ventilation; Exercise intolerance; Muscle dysfunction; Chronic pulmonary obstructive disease; Muscle afferents
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: SPINAL-20520